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<h2 class="element-invisible">You are here</h2><div class="breadcrumb"><a href="/">Home</a> » <a href="/news-events">News & Events</a> » <a href="/news-events/nih-research-matters">NIH Research Matters</a></div> <div class="l-region l-region--section-header">
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<p class="publishdate"><span property="dc:date" datatype="xsd:dateTime" content="2021-05-25T00:00:00-04:00" class="date-display-single">May 25, 2021</span></p><div class='syndicate'><h1>Airway-on-a-chip screens drugs for use against COVID-19</h1><div class="callout callout-with-border"><h3>At a Glance</h3>
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<ul>
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<li>Researchers used an airway-on-a-chip that mimics living lung tissue to screen approved drugs for use against SARS-CoV-2.</li>
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<li>The most effective drug identified, called amodiaquine, is now part of a clinical trial of treatments for COVID-19.</li>
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</ul></div><div class="media-float-right"><div class="ds-1col file file-image file-image-jpeg view-mode-floated_media clearfix">
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<picture title="Close-up photograph of chip with several tubes attached">
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<!--[if IE 9]><video style="display: none;"><![endif]-->
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-large/public/news-events/research-matters/2021/20210525-lung-on-chip.jpg?itok=ROqKb5x2&timestamp=1621953143 1x" media="screen and (min-width: 960px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2021/20210525-lung-on-chip.jpg?itok=zzFfRInq&timestamp=1621953143 1x" media="screen and (min-width: 800px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium-small/public/news-events/research-matters/2021/20210525-lung-on-chip.jpg?itok=bP2cMbBv&timestamp=1621953143 1x" media="screen and (min-width: 600px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-small/public/news-events/research-matters/2021/20210525-lung-on-chip.jpg?itok=5lUe4jbX&timestamp=1621953143 1x" media="screen and (min-width: 480px)" />
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<source srcset="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-tiny/public/news-events/research-matters/2021/20210525-lung-on-chip.jpg?itok=eGU6x2md&timestamp=1621953143 1x" media="screen and (min-width: 0)" />
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<!--[if IE 9]></video><![endif]-->
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<img src="https://www.nih.gov/sites/default/files/styles/floated_media_breakpoint-medium/public/news-events/research-matters/2021/20210525-lung-on-chip.jpg?itok=zzFfRInq&timestamp=1621953143" alt="Close-up photograph of chip with several tubes attached" title="Close-up photograph of chip with several tubes attached" />
|
||
</picture><span class="caption">This lung-on-a-chip serves as a model of human lungs to test for drug safety and efficacy.</span><span class="credit">Wyss Institute for Biologically Inspired Engineering, Harvard University</span></div>
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||
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||
</div><p>The identification of SARS-CoV-2, the virus that causes COVID-19, in January 2020 started an international rush to find drugs that could prevent or treat infection. One potential shortcut to COVID-19 therapies is to test drugs that have already been approved for other conditions. Such repurposing of existing drugs can greatly speed the time required for human clinical trials.</p>
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||
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||
<p>To screen drugs against viruses like SARS-CoV-2, researchers often use human cell lines grown in the lab. These are easy to work with and relatively inexpensive. However, they can’t replicate the complex environment of a living organ, such as the lungs. Sometimes, drugs that work in cell lines prove ineffective—or even do harm—when later tested in people. <a href="https://www.nih.gov/news-events/nih-research-matters/hydroxychloroquine-doesnt-benefit-hospitalized-covid-19-patients">Hydroxychloroquine</a> is one such example.</p>
|
||
|
||
<p>To help overcome this challenge, a research team led by Dr. Donald Ingber from the Wyss Institute at Harvard University has been developing organ chips for more accurate screening of drugs to treat infections. These chips, which are about the size of a USB memory stick, provide an environment that can grow many cell types in close contact with each other. This allows the cells to form tissues and interfaces between tissues that mimic those found within the body.</p>
|
||
|
||
<p>The team grew lung tissue on an Airway Chip that included cells that line the lung airway, blood vessel cells, and even immune system cells. The tissue that grew on the chips mimicked traits seen in living lungs, such as mucus production and inflammation.</p>
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<div class="media-float-right"><div class="media media-element-container media-shadowbox_sidebar"><div class="ds-1col file file-image file-image-jpeg view-mode-shadowbox_sidebar clearfix">
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<a href="https://www.nih.gov/sites/default/files/news-events/research-matters/2021/20210525-lung-fig-1a.jpg"><img title="Schematic of the Airway Chip shows the air channel, blood channel, and the different tissue layers between them. " class="media-element" data-delta="5" typeof="foaf:Image" src="https://www.nih.gov/sites/default/files/news-events/research-matters/2021/20210525-lung-fig-1a.jpg" width="1041" height="483" alt="Schematic of the Airway Chip shows the air channel, blood channel, and the different tissue layers between them. " /></a><span class="caption">Schematic of the Airway Chip shows the air channel, blood channel, and the different tissue layers between them. (Click image to enlarge.)</span><span class="credit">Ingber lab, Nature Biomedical Engineering</span></div>
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</div></div>
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<p>In their new study, the scientists used the Airway Chip to screen drugs for use against influenza and SARS-CoV-2. The work was funded in part by NIH’s National Center for Advancing Translational Sciences (NCATS). Results were published on May 3, 2021, in <em>Nature Biomedical Engineering</em>.</p>
|
||
|
||
<p>In proof-of-concept studies using several influenza viruses, the lung tissues in the Airway Chip showed the same types of damage after viral exposure as seen in living lungs. The drug oseltamivir, better known as Tamiflu, blocked flu virus replication in the chips over the same time period as that seen when used in people.</p>
|
||
|
||
<p>The team next tested drugs that were approved for other conditions for their ability to boost the effects of oseltamivir. They found that one such drug called nafamostat helped suppress infection, doubling the time window in which oseltamivir could be effectively used.</p>
|
||
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||
<p>Pivoting their efforts to COVID-19, the researchers then used the chips to identify three approved drugs—amodiaquine, toremifene, and clomiphene—that could reduce SARS-CoV-2 entry into human lung cells. In contrast, hydroxychloroquine was among other drugs that, while working in cell lines, had no effect when tested in the Airway Chip. The team chose the most potent, amodiaquine, for further testing.</p>
|
||
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||
<p>In hamsters, amodiaquine blocked the transmission of SARS-CoV-2 from infected to uninfected animals by 90%. When used after exposure as a treatment, the drug reduced the amount of virus in the body by about 70%. Based in part on these results, amodiaquine has been incorporated into the ongoing ANTICOV clinical trial, which is testing drugs to treat COVID-19 in 13 African countries.</p>
|
||
|
||
<p>“Thanks to the openness and collaboration that the pandemic has sparked within the scientific community, our lead drug is now being tested in humans,” Ingber says. “It’s a powerful testament to Organ Chips’ ability to accelerate preclinical testing.”</p>
|
||
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||
<p>—by Sharon Reynolds</p></div><h2 class="label-above">Related Links</h2><ul class="spaced print-urls"><li><a href="https://www.nih.gov/news-events/nih-research-matters/oral-antiviral-drug-effective-against-covid-19-hamsters" target="_top">Oral Antiviral Drug Effective Against COVID-19 in Hamsters</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/nanoparticle-based-flu-vaccine" target="_top">Nanoparticle-Based Flu Vaccine</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/immune-response-vaccination-after-covid-19" target="_top">Immune Response to Vaccination After COVID-19</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/sars-cov-2-antibodies-protect-reinfection" target="_top">SARS-CoV-2 Antibodies Protect from Reinfection</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/experimental-coronavirus-vaccine-highly-effective" target="_top">Experimental Coronavirus Vaccine Highly Effective</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/final-report-confirms-remdesivir-benefits-covid-19" target="_top">Final Report Confirms Remdesivir Benefits for Covid-19</a></li><li><a href="https://www.nih.gov/news-events/nih-research-matters/computer-designed-proteins-may-protect-against-coronavirus" target="_top">Computer-Designed Proteins May Protect Against Coronavirus</a></li><li><a href="https://www.nih.gov/news-events/news-releases/nih-awards-15-million-support-development-3-d-human-tissue-models" target="_top">NIH Awards $15 Million to Support Development of 3-D Human Tissue Models</a></li><li><a href="https://covid19.nih.gov/" target="_top">Coronavirus (COVID-19)</a></li><li><a href="https://www.coronavirus.gov/" target="_top">Coronavirus (COVID-19) (CDC)</a></li></ul><p class="footnote"><strong class="label-inline">References: </strong><a href="https://pubmed.ncbi.nlm.nih.gov/33941899/">A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics.</a> Si L, Bai H, Rodas M, Cao W, Oh CY, Jiang A, Moller R, Hoagland D, Oishi K, Horiuchi S, Uhl S, Blanco-Melo D, Albrecht RA, Liu WC, Jordan T, Nilsson-Payant BE, Golynker I, Frere J, Logue J, Haupt R, McGrath M, Weston S, Zhang T, Plebani R, Soong M, Nurani A, Kim SM, Zhu DY, Benam KH, Goyal G, Gilpin SE, Prantil-Baun R, Gygi SP, Powers RK, Carlson KE, Frieman M, tenOever BR, Ingber DE. <em>Nat Biomed Eng</em>. 2021 May 3. doi: 10.1038/s41551-021-00718-9. Online ahead of print. PMID: 33941899.</p><p class="footnote"><strong class="label-inline">Funding: </strong>NIH’s National Center for Advancing Translational Sciences (NCATS); Defense Advanced Research Projects Agency; Bill and Melinda Gates Foundation; Marc Haas Foundation; Wyss Institute for Biologically Inspired Engineering.</p>
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